This application is based on German Application DE 199 05 685.4, filed Feb. 11, 1999, the disclosure of which is incorporated in its entirety herein by reference.
The invention relates to an improved process for the production of 2,3,5-trimethylhydroquinone diesters by rearrangement of 2,6,6-trimethyl-2-cyclohexene-1,4-dione (4-oxoisophorone, ketoisophorone) in the presence of a dissolved, acidic catalyst and an acylating agent, such as, for example, carboxylic anhydrides or carboxylic acid halides. The 2,3,5-trimethylhydroquinone diester can thereafter, optionally, be saponified to give free 2,3,5-trimethylhydroquinone (TMHQ), which is a valuable building block in the synthesis of vitamin E. 
2,3,5-Trimethylhydroquinone diesters and the corresponding TMHQ are important intermediates which are used in the production of vitamin E and vitamin E acetate. In addition to the known production process based on aromatic starting materials, 2,3,5-trimethylhydroquinone can be produced from a non-aromatic compound, 2,6,6-trimethyl-2-cyclohexene-1,4-dione, by rearrangement under acylating conditions and subsequent hydrolysis.
In patent specification DE 26 46 172 C2, a process is described in which 2,6,6-trimethyl-2-cyclohexene-1,4-dione is rearranged directly to trimethylhydroquinone in the vapor phase at a high temperature in contact with an acidic catalyst. However, the yield in this process is only low (50% with 30% conversion). If the aromatization of 2,6,6-trimethyl-2-cyclohexene-1,4-dione is carried out in the presence of an acylating agent, trimethylhydroquinone diesters are obtained which lead to trimethylhydroquinone by subsequent hydrolysis.
According to Bull. Korean. Chem. Soc. 1991, 12, 253, for example, the rearrangement is performed in a 5% solution in acetic anhydride by adding five equivalents of concentrated sulfuric acid. However, trimethylhydroquinone diester is only obtained in a 30% yield in this process.
In another process according to DE-OS 2 149 159, 2,6,6-trimethyl-2-cyclohexene-1,4-dione can be converted in the presence of acetic anhydride in a rearrangement catalyzed by protonic or Lewis acids to trimethylhydroquinone diacetate which is then saponified to trimethylhydroquinone.
Although by this method yields and conversions of ketoisophorone are is moderate to good (maximum 66% TMHQ yield, based on ketoisophorone used), large quantities of strong acids (up to 150 mole % based on ketoisophorone) and large excesses of acetic anhydride (5-10 moles Ac2O/1 mole ketoisophorone) are used, which makes the process unattractive from an industrial point of view.
According to a more recent process (DE-OS 196 27 977), ketoisophorone is converted to the diester in the presence of only a double stoichiometric acetic anhydride equivalent with homogeneously dissolved super acids (H0 less than xe2x88x9211.9) as catalysts in the liquid phase. Particularly high selectivities are achieved with trifluoromethanesulfonic acid, chlorosulfonic acid and oleum of various SO3 concentrations. A disadvantage of this process is the use of the above catalysts, the corrosive nature of which causes considerable material problems. The use of trifluoromethanesulfonic acid as catalyst is expensive and difficult, as this acid is complicated to handle and the reagent can only be partly recycled.
An object of the invention is to provide an improved process for the production of 2,6,6-trimethyl-2-cyclohexene-1,4-dione diesters, which, in particular, proceeds using an easily handled, economical catalyst. The corresponding hydroquinones can optionally be obtained from the esters by hydrolysis.
The invention provides a process for the production of trimethylhydroquinone diesters, 
wherein R, R1 are the same or different, by reacting 2,6,6-trimethyl-2-cyclohexene-1,4-dione(ketoisophorone or KIP) 
with an acylating agent in the presence of catalytic quantities of a protonic acid, which is characterized in that orthoboric acid and/or boron oxide on the one hand and one or more carboxylic acid(s), selected from the group of hydroxycarboxylic acids, di- or tricarboxylic acids, which optionally also contain hydroxy groups, on the other hand, are used.
This combined catalyst system is extraordinarily economical and is also easy to handle.
At the same time, yields and selectivities can be regarded as equivalent to those known from the prior art.
The activity of the catalyst system is based on a catalyst species formed in situ from the boron-containing compound and the carboxylic acids, the pKS value of which is lower than the pKS value of boric acid.
This catalyst combination is preferably used in a quantity of 0.1 to 10 mole %, based on the ketoisophorone used. It is present in the reaction mixture in dissolved form.
Many different boron compounds can be used as the boric acid derivative, especially boric acid triesters, boron oxides and boric acid, boric acid being used as the particularly preferred catalyst. Various oligofunctional compounds which react with boric acid derivatives, increasing the co-ordination sphere of boron, to form stable, complex boric acids, the acidic strength of which is stronger than that of the corresponding free boric acid, can be used as co-catalyst.
The ratio of boron component to co-catalyst can be varied within ranges between 1:1 and 1:10 (molar ratio), a ratio of 1:2 being particularly preferred in the case of bifunctional co-catalysts. The active catalyst species is formed in situ by reaction of the binary catalyst system of boric acid derivative and the co-catalyst in the presence of the acylating agent.
In particular, hydroxy acids of the general formula
R2xe2x80x94CO2Hxe2x80x83xe2x80x83(I),
in which:
R2 represents aryl, especially phenylene, naphthyl, each substituted by OH, HOxe2x80x94(CH2)qxe2x80x94, CH3(CHOH)n(CH2)mxe2x80x94, where
m is an integer from 0 to 20, preferably 0 to 8, and
n: an integer from 1 to 5, especially 1 to 4,
q: an integer from 1 to 6
are designated as co-catalysts.
The particularly suitable hydroxycarboxylic acids include glycolic acid, lactic acid, mandelic acid, tartaric acid (regardless of the configuration), citric acid, especially salicylic acid or acetylsalicylic acid, but also hydroxyl group-containing amino acids such as serine or threonine and aldonic acid.
Dicarboxylic acids of the general formula
HO2Cxe2x80x94R3xe2x80x94CO2Hxe2x80x83xe2x80x83(II),
in which:
R3 represents aryl, especially phenylene, naphthyl, (CH2)m, wherein m has the same meaning as above, or (CH2)m(CHX)r, wherein r represents an integer from 1 to 5, and X is OH,H or (CH2)Pxe2x80x94(CX)(COOH)xe2x80x94(CH2)P with P=1 to 3 or alkenyl having C2 to C6,
are also preferably used.
Oxalic acid, malonic acid, malic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, especially oxalic acid, and aromatic dicarboxylic acids such as phthalic acid, isophthalic acid and terephthalic acid and 2,6-naphthalene-carboxylic acid or tricarboxylic acids such as trimesic acid or citric acid, and unsaturated dicarboxylic acids such as fumaric acid and maleic acid, but also polyhydroxydicarboxylic acids, are particularly suitable.
As acylating agent, compounds of the general formula: 
are preferably used, in which:
R, R1, are the same or different and represent an optionally substituted, aliphatic, alicyclic C1 to C20 group, especially an aliphatic C2 to C4 group, or an aryl group, preferably phenylene.
The anhydride of acetic acid is particularly suitable.
Other suitable anhydrides are those of propionic acid, butyric acid, isobutyric acid, cyclohexane-carboxylic acid or benzoic acid.
The anhydrides of chloroacetic acid, trihaloacetic acid or trifluoromethansulfonic acid can also be used, even if they are not preferred.
The ratio between ketoisophorone and acylating agent can be varied within broad ranges, but a KIP/acylating agent ratio of 1:2 to 1:3 is particularly preferred. Other acylating reagents such as carboxylic acid halides, especially chlorides, enol esters and diketene corresponding to the above-mentioned anhydrides, can also be used as a synthesis equivalent and substitute for the preferably used acetic anhydride.
The process according to the invention can be carried out using inert organic solvents. The concentration of the reactants in the solvent has only an insignificant effect on the product profile of the reaction. It is particularly preferable to work without solvents, so that costly reprocessing operations or solvent recycling steps are avoided.
If the rearrangement takes place in the presence of organic solvents, suitable representative solvents are aliphatic and cyclic esters, e.g. ethyl acetate, propyl acetate, isopropyl acetate and xcex3-butyrolactone; hydrocarbons, for example hexane, heptane, toluene and xylene; and ketones, for example isobutyl methyl ketone, diethyl ketone and isophorone.
The KIP rearrangement takes place at temperatures of between xe2x88x9280xc2x0 and +150xc2x0 C., a temperature range of between xe2x88x9230xc2x0 and +50xc2x0 C. being particularly preferred. At even higher temperatures, by-product formation increases at the expense of the trimethylhydroquinone ester.
In one embodiment of the process according to the invention, the trimethylhydroquinone diester formed is crystallized directly from the carboxylic acid formed during the reaction. However, it is also possible to perform the isolation by adding a suitable solvent after distilling off the free carboxylic acid.
In another embodiment, the TMHQ diacetate formed is saponified without isolation, by adding water to the raw rearrangement mixture. The same catalyst already used for the rearrangement of ketoisophorone can be used as the saponification catalyst. The free trimethylhydroquinone is isolated by a method which is known per se, by crystallization from a suitable medium.
Trimethylhydroquinone synthesis has thus been successfully raised to a technically achievable, economical level by the provision of a reasonable, readily accessible, easy to handle catalyst system based on a boric acid derivative and operation as a cyclic process with catalyst recycling.
The production of 2,3,5-trimethylhydroquinone diesters and 2,3,5-trimethylhydroquinone according to the invention has the following substantial advantages compared with the prior art.
The yields of 2,3,5-trimethylhydroquinone diesters and 2,3,5-trimethylhydroquinone are among the highest values that can be achieved with trifluoromethanesulfonic acid as catalyst, with a yield of up to 95%, based on the ketoisophorone used.
Compared with the super acids known from the prior art, the catalyst has substantial handling advantages in terms of dosing, toxicity and corrosive properties. Thus, the catalyst can be produced by simply stirring together the catalyst components before use, or it is formed in situ by successive addition of the components to the carboxylic anhydride.